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New Indications for Teduglutide in Temporary Intestinal Failure Patients
versus 28.89% of control subjects [OR 0.37 (0.14-1), p 0.05]. CONCLUSION: These results suggest an inverse relationship between Ulcerative Colitis and colonic diverticulosis.
NICKEL ALLERGIC CONTACT MUCOSITIS: DUODENAL HISTOLOGICAL, IMMUNOHISTOCHEMICAL AND CULTURAL CHARACTERIZATION OF AN EMERGING CLINICOPATHOLOGIC ENTITY Raffaele Borghini, Mariacatia Marino, Rossella Casale, Marco Di Tola, Barbara Porowska, Vincenzo Villanacci, Antonio Tiberti, Giuseppe Donato, Antonio Picarelli BACKGROUND: The estimated prevalence of Nickel (Ni) sensitization is 30% in Europe. Alimentary Ni can be considered responsible of IBS-like disorders as Allergic Contact Mucositis (ACM). An involvement of TLR4 has been recently showed in its immunological characterization. A local adaptive response in Ni-sensitive patients has been suggested, with CD3+ lymphocytes highlighted in oral mucosa biopsy samples. Moreover, a Ni-induced production of IL-10 and IFN-γ has been showed in peripheral blood mononuclear cells' cultures. Recently, a Ni oral mucosa patch test (omPT) has been proposed for Ni MAC diagnosis. AIM: We wanted to evaluate histological and immunohistochemical features in duodenal biopsies taken from Ni-sensitive patients. Inflammatory characterization has also been investigated in culture supernatant of duodenal biopsies. MATHERIALS AND METHODS: 9 symptomatic Ni-sensitive patients (group A) were studied after a specific symptom questionnaire and a positive Ni omPT, confirming Ni ACM. 9 control patients (group B) with dyspepsia and GERD were recruited in absence of Ni-related symptoms, as proved by questionnaire and a negative Ni omPT. All patients underwent EGD and duodenal biopsies collection. Histology and immunohistochemistry (with CD3+, CD4+ and CD8+ lymphocytes count) were performed. Culture supernatants of duodenal biopsies were performed to determine IL-10 and IFN-γ levels with and without Ni sulfate stimulation. RESULTS: All duodenal sections from group A showed class 0 according Marsh-Oberhuber; 3-4 eosinophils per field (400x) were detected in the lamina propria; 17.7 ± 2.9 CD3+ IELs/100 ECs were detected (4.5 ± 2.1 CD4+; 13.2 ± 3.4 CD8+); lymphocytes were grouped in clusters in surface epithelium and in a linear way at the base of the villi. IFN-γ levels in cultures from group A were significantly higher after stimulation with Ni than without Ni (p = 0.0116). IL-10 levels in group A cultures were significantly lower after stimulation with Ni, rather than without Ni (p = 0.0010). Control patients showed no statistically significant difference in cultural IFN-γ and IL-10 levels. DISCUSSION: No specific histological and immunohistochemical alterations have been found in Ni-sensitive patients, apart from a peculiar arrangement of T lymphocytes. The absence of Ni seems to guarantee an immunological tolerance in Ni-sensitive patients, with increased IL-10 and reduced IFN-γ levels in cultures. On the other hand, exposure to Ni seems to invert this state. These results seem to confirm and extend previous data about Ni ACM.
Mo1893 NEW INDICATIONS FOR TEDUGLUTIDE IN TEMPORARY INTESTINAL FAILURE PATIENTS Betty Li, Kelly Galen, Johan F Nordenstam, Anders Mellgren, Vivek Chaudhry, William J Ennis, Cemal Yazici, Robert Carroll Background: Teduglutide (GattexTM) is a novel analog of naturally occurring human glucagon-like peptide 2 (GLP-2), demonstrated to promote the regeneration and repair of intestinal epithelium. Beneficial effects include expansion of villus height and reduced intestinal permeability. Teduglutide is presently only indicated for adults with short bowel syndrome (SBS), who have been dependent on parenteral nutrition (PN) support for 12 months or longer. However, there are patients, who do not meet these criteria, but still may benefit from the growth effect the drug has on the intestinal mucosa. Given the intestinotrophic mechanisms of teduglutide, we hypothesized it has the potential to improve outcomes in these patients as well. Aim: To evaluate the use of teduglutide beyond its approved indications and to discuss the results of this adjunctive treatment in patients resistant to established therapy. Methods: We reviewed 3 patients, in whom teduglutide was used off-label. Patients were followed clinically, medical records were reviewed and a literature research was conducted. Clinical evolution was followed from the first administration of teduglutide to present. Results: Teduglutide was used off-label in three patients. All three patients received the FDA approved dosing of 0.05 mg/kg subcutaneous daily. The first case was a patient with severe Crohn's Disease (CD) complicated by a persistent colocutaneous fistula. Teduglutide was prescribed as subcutaneous injections at a daily dose of 0.05 mg/kg. Patient only required PN for 1 month, and after 8 months of teduglutide therapy, the patient demonstrated complete fistula closure. The second case was a patient with CD complicated by severe malnutrition after surgery for recurrent bowel obstruction. Due to previous severe adverse effects from PN, teduglutide was considered. Patient gained 3 kgs after 6 weeks of teduglutide. Patient was continued on tedugludtide for over 2 years, and maintained satisfactory weight and did not require PN. The third case was a patient with malabsorption, secondary to a high output diverting ileostomy, contributing to impaired healing of a stage IV decubitus ulcer. After 2 months of therapy, the patient's requirement for magnesium supplementation decreased, pre-albumin increased by 250%, and the ulcer had decreased by 40%; this enabled a simpler and better surgical closure of the wound . Conclusion: These cases demonstrate that teduglutide may have beneficial effects in a wider group of patients not meeting the strict criteria for intestinal failure and lifelong PN. Further studies are needed to evaluate the efficacy of teduglutide in patients who may require short-term small bowel rehabilitation and/or have chronically impaired absorptive capacity but not requiring full PN support.
Mo1896 ELEVATED CLINICAL INFLAMMATORY MARKERS AND CYTOKINE EXPRESSION IN PERI- DIVERTICULAR COLONIC TISSUE IN PATIENTS POST COMPLICATED VERSUS UNCOMPLICATED ACUTE DIVERTICULITIS Adi Lahat, Miri Yavzori, Orit Picard, Shomron Ben Horin, Background Recent data suggest continuous chronic inflammation in patients post complicated acute diverticulitis (AD). Aim To compare clinical parameters and inflammatory cytokine expression between patients post complicated and uncomplicated AD. Patients and methods Sixteen patients post AD were included, of them 8 suffered from complicated disease. Demographic data, disease characteristics and inflammatory markers were collected. Patients underwent colonoscopy with Diverticular Inflammation and Complication Assessment (DICA). During colonoscopy tissue samples from diverticular and healthy tissue were obtained. Expression of various inflammatory cytokines mRNA was measured using RTPCR. Results Clinically, patients post complicated AD had significantly higher CRP levels ( 9.85 ±7.5 vs 3±2.1 p=0.027) and tendency for higher calprotectin levels (115.7±85 vs 35±8.7, p=0.08). All other parameters ( age, attacks number, WBC count, time from last attack, DICA score) did not differ between groups. Table 1 shows differences in cytokine expression between healthy and diverticular tissue in both groups. Conclusions: Patients post complicated AD have higher inflammatory markers than patients post uncomplicated AD, and significantly higher inflammatory cytokine levels in diverticular colonic tissue compared to healthy tissue and to diverticular and healthy tissue of patients post uncomplicated AD. - cytokine expression in affected vs healthy colonic tissue in patients post complicated AD versus uncomplicated AD
Mo1894 PREVALENCE OF COLONIC DIVERTICULOSIS IN PATIENTS WITH ULCERATIVE COLITIS Juan S. Lasa, Liliana N. Spallone, Silvina M. Gandara, Claudia A. Cadiz, Claudia M. Buenavida, Norma Gallo, Saul S. Berman, Elsa C. Chaar, David H. Zagalsky BACKGROUND: The etiology of colonic diverticulosis is not clearly known; recent evidence suggest that changes in intestinal microbiota might be involved. Coincidentally, inflammatory bowel disease such as Ulcerative Colitis has also been linked to intestinal microbiota alterations. However, these two entities may not always coincide. The true prevalence of diverticulosis in patients with Ulcerative Colitis is not well known. AIM: To compare the prevalence of colonic diverticulosis in adult patients with Ulcerative Colitis versus asymptomatic subjects MATERIALS AND METHODS: A retrospective nested case-control study was designed. Adult patients with Ulcerative Colitis referred for colonoscopy were recruited as cases. Age and gender-matched asymptomatic subjects referred for screening colonoscopy were recruited as controls in a 2:1 fashion. Colonic diverticulosis prevalence as well as its extension was compared between groups. Chi square test was used to compare categorical variables. Numerical variables were compared by means of Student's t test. A p value of less than 0.05 was considered as statistically significant. RESULTS: Between January 2014 and July 2016, 45 patients with Ulcerative Colitis undertook colonoscopy and were regarded as cases. These patients were compared against 90 control subjects. Median age was 47 years (range 3075) and 54% were male. Mayo Endoscopic Score in Ulcerative Colitis subjects was I in 55.5% and II in 44.5% patients. Most patients (66.6%) showed proctosigmoiditis or leftsided colitis. Overall, 13.33% of Ulcerative Colitis patients showed colonic diverticulosis
S-813
AGA Abstracts
AGA Abstracts
Mo1895
NICKEL ALLERGIC CONTACT MUCOSITIS: DUODENAL HISTOLOGICAL, IMMUNOHISTOCHEMICAL AND CULTURAL CHARACTERIZATION OF AN EMERGING CLINICOPATHOLOGIC ENTITY Raffaele Borghini, Mariacatia Marino, Rossella Casale, Marco Di Tola, Barbara Porowska, Vincenzo Villanacci, Antonio Tiberti, Giuseppe Donato, Antonio Picarelli BACKGROUND: The estimated prevalence of Nickel (Ni) sensitization is 30% in Europe. Alimentary Ni can be considered responsible of IBS-like disorders as Allergic Contact Mucositis (ACM). An involvement of TLR4 has been recently showed in its immunological characterization. A local adaptive response in Ni-sensitive patients has been suggested, with CD3+ lymphocytes highlighted in oral mucosa biopsy samples. Moreover, a Ni-induced production of IL-10 and IFN-γ has been showed in peripheral blood mononuclear cells' cultures. Recently, a Ni oral mucosa patch test (omPT) has been proposed for Ni MAC diagnosis. AIM: We wanted to evaluate histological and immunohistochemical features in duodenal biopsies taken from Ni-sensitive patients. Inflammatory characterization has also been investigated in culture supernatant of duodenal biopsies. MATHERIALS AND METHODS: 9 symptomatic Ni-sensitive patients (group A) were studied after a specific symptom questionnaire and a positive Ni omPT, confirming Ni ACM. 9 control patients (group B) with dyspepsia and GERD were recruited in absence of Ni-related symptoms, as proved by questionnaire and a negative Ni omPT. All patients underwent EGD and duodenal biopsies collection. Histology and immunohistochemistry (with CD3+, CD4+ and CD8+ lymphocytes count) were performed. Culture supernatants of duodenal biopsies were performed to determine IL-10 and IFN-γ levels with and without Ni sulfate stimulation. RESULTS: All duodenal sections from group A showed class 0 according Marsh-Oberhuber; 3-4 eosinophils per field (400x) were detected in the lamina propria; 17.7 ± 2.9 CD3+ IELs/100 ECs were detected (4.5 ± 2.1 CD4+; 13.2 ± 3.4 CD8+); lymphocytes were grouped in clusters in surface epithelium and in a linear way at the base of the villi. IFN-γ levels in cultures from group A were significantly higher after stimulation with Ni than without Ni (p = 0.0116). IL-10 levels in group A cultures were significantly lower after stimulation with Ni, rather than without Ni (p = 0.0010). Control patients showed no statistically significant difference in cultural IFN-γ and IL-10 levels. DISCUSSION: No specific histological and immunohistochemical alterations have been found in Ni-sensitive patients, apart from a peculiar arrangement of T lymphocytes. The absence of Ni seems to guarantee an immunological tolerance in Ni-sensitive patients, with increased IL-10 and reduced IFN-γ levels in cultures. On the other hand, exposure to Ni seems to invert this state. These results seem to confirm and extend previous data about Ni ACM.
Mo1893 NEW INDICATIONS FOR TEDUGLUTIDE IN TEMPORARY INTESTINAL FAILURE PATIENTS Betty Li, Kelly Galen, Johan F Nordenstam, Anders Mellgren, Vivek Chaudhry, William J Ennis, Cemal Yazici, Robert Carroll Background: Teduglutide (GattexTM) is a novel analog of naturally occurring human glucagon-like peptide 2 (GLP-2), demonstrated to promote the regeneration and repair of intestinal epithelium. Beneficial effects include expansion of villus height and reduced intestinal permeability. Teduglutide is presently only indicated for adults with short bowel syndrome (SBS), who have been dependent on parenteral nutrition (PN) support for 12 months or longer. However, there are patients, who do not meet these criteria, but still may benefit from the growth effect the drug has on the intestinal mucosa. Given the intestinotrophic mechanisms of teduglutide, we hypothesized it has the potential to improve outcomes in these patients as well. Aim: To evaluate the use of teduglutide beyond its approved indications and to discuss the results of this adjunctive treatment in patients resistant to established therapy. Methods: We reviewed 3 patients, in whom teduglutide was used off-label. Patients were followed clinically, medical records were reviewed and a literature research was conducted. Clinical evolution was followed from the first administration of teduglutide to present. Results: Teduglutide was used off-label in three patients. All three patients received the FDA approved dosing of 0.05 mg/kg subcutaneous daily. The first case was a patient with severe Crohn's Disease (CD) complicated by a persistent colocutaneous fistula. Teduglutide was prescribed as subcutaneous injections at a daily dose of 0.05 mg/kg. Patient only required PN for 1 month, and after 8 months of teduglutide therapy, the patient demonstrated complete fistula closure. The second case was a patient with CD complicated by severe malnutrition after surgery for recurrent bowel obstruction. Due to previous severe adverse effects from PN, teduglutide was considered. Patient gained 3 kgs after 6 weeks of teduglutide. Patient was continued on tedugludtide for over 2 years, and maintained satisfactory weight and did not require PN. The third case was a patient with malabsorption, secondary to a high output diverting ileostomy, contributing to impaired healing of a stage IV decubitus ulcer. After 2 months of therapy, the patient's requirement for magnesium supplementation decreased, pre-albumin increased by 250%, and the ulcer had decreased by 40%; this enabled a simpler and better surgical closure of the wound . Conclusion: These cases demonstrate that teduglutide may have beneficial effects in a wider group of patients not meeting the strict criteria for intestinal failure and lifelong PN. Further studies are needed to evaluate the efficacy of teduglutide in patients who may require short-term small bowel rehabilitation and/or have chronically impaired absorptive capacity but not requiring full PN support.
Mo1896 ELEVATED CLINICAL INFLAMMATORY MARKERS AND CYTOKINE EXPRESSION IN PERI- DIVERTICULAR COLONIC TISSUE IN PATIENTS POST COMPLICATED VERSUS UNCOMPLICATED ACUTE DIVERTICULITIS Adi Lahat, Miri Yavzori, Orit Picard, Shomron Ben Horin, Background Recent data suggest continuous chronic inflammation in patients post complicated acute diverticulitis (AD). Aim To compare clinical parameters and inflammatory cytokine expression between patients post complicated and uncomplicated AD. Patients and methods Sixteen patients post AD were included, of them 8 suffered from complicated disease. Demographic data, disease characteristics and inflammatory markers were collected. Patients underwent colonoscopy with Diverticular Inflammation and Complication Assessment (DICA). During colonoscopy tissue samples from diverticular and healthy tissue were obtained. Expression of various inflammatory cytokines mRNA was measured using RTPCR. Results Clinically, patients post complicated AD had significantly higher CRP levels ( 9.85 ±7.5 vs 3±2.1 p=0.027) and tendency for higher calprotectin levels (115.7±85 vs 35±8.7, p=0.08). All other parameters ( age, attacks number, WBC count, time from last attack, DICA score) did not differ between groups. Table 1 shows differences in cytokine expression between healthy and diverticular tissue in both groups. Conclusions: Patients post complicated AD have higher inflammatory markers than patients post uncomplicated AD, and significantly higher inflammatory cytokine levels in diverticular colonic tissue compared to healthy tissue and to diverticular and healthy tissue of patients post uncomplicated AD. - cytokine expression in affected vs healthy colonic tissue in patients post complicated AD versus uncomplicated AD
Mo1894 PREVALENCE OF COLONIC DIVERTICULOSIS IN PATIENTS WITH ULCERATIVE COLITIS Juan S. Lasa, Liliana N. Spallone, Silvina M. Gandara, Claudia A. Cadiz, Claudia M. Buenavida, Norma Gallo, Saul S. Berman, Elsa C. Chaar, David H. Zagalsky BACKGROUND: The etiology of colonic diverticulosis is not clearly known; recent evidence suggest that changes in intestinal microbiota might be involved. Coincidentally, inflammatory bowel disease such as Ulcerative Colitis has also been linked to intestinal microbiota alterations. However, these two entities may not always coincide. The true prevalence of diverticulosis in patients with Ulcerative Colitis is not well known. AIM: To compare the prevalence of colonic diverticulosis in adult patients with Ulcerative Colitis versus asymptomatic subjects MATERIALS AND METHODS: A retrospective nested case-control study was designed. Adult patients with Ulcerative Colitis referred for colonoscopy were recruited as cases. Age and gender-matched asymptomatic subjects referred for screening colonoscopy were recruited as controls in a 2:1 fashion. Colonic diverticulosis prevalence as well as its extension was compared between groups. Chi square test was used to compare categorical variables. Numerical variables were compared by means of Student's t test. A p value of less than 0.05 was considered as statistically significant. RESULTS: Between January 2014 and July 2016, 45 patients with Ulcerative Colitis undertook colonoscopy and were regarded as cases. These patients were compared against 90 control subjects. Median age was 47 years (range 3075) and 54% were male. Mayo Endoscopic Score in Ulcerative Colitis subjects was I in 55.5% and II in 44.5% patients. Most patients (66.6%) showed proctosigmoiditis or leftsided colitis. Overall, 13.33% of Ulcerative Colitis patients showed colonic diverticulosis
S-813
AGA Abstracts
AGA Abstracts
Mo1895